The Fenical component (Laboratory Program #2) of the National Cooperative Natural Products Drug Discovery Group (NCNPDDG) entitled "Anticancer Agents from Cultured and Collected Marine Organisms," will approach the isolation of new anticancer agents utilizing selected marine invertebrates and cultured marine bacteria found in association, probably symbiotic, with marine plants and invertebrates. The specific goal of this proposal remains the isolation and characterization of structurally unique and pharmacologically novel antitumor agents. This research component is a collaborative effort involving the Oncology Drug Discovery Group at Bristol-Myers Squibb, Pharmaceutical Research Institute (both at their Princeton, NJ and Wallingford, CT locations), and Fenical group researchers at the Scripps Institution of Oceanography. An additional collaboration, between researchers at the Silliman University Marine Laboratory, Dumaguete City, Philippines, will provide access to what is, without question, the richest marine environment known. This program will investigate selected marine organisms (excluding sponges, see Faulkner Laboratory Program #1) which have proven to be unique sources of anticancer agents. Our Philippine collections will thus emphasize ascidians, octocorals, bryozoans, anthozoans and related invertebrates, which are in abundance in Philippine waters. Ascidians, in particular, appear promising as sources of antitumor agents, as they are chemically rich and found in abundance within Philippine waters (ca. 30-40% of the collections!). The microbiological aspect of this program will focus on marine bacteria which are symbiotic with Philippine marine plants and invertebrates. As part of the Silliman collecting program, we will isolate and culture the bacteria found in association with many invertebrates. Novel media, and conditions for isolation and culture, have recently been under development. These new methods should allow access to a diverse, highly specific, and previously unknown microbial flora. Extracts of invertebrates and culture broths (expected to reach ca. 2,000 each year) will be evaluated at BMS: and new lead extracts will be fractionated by standard bioassay-guided methods. When needed, large-scale fermentations (ca. 2,000 liters) will be provided by Bristol-Myers Squibb.